HIV 血脑屏障穿透性和抗逆转录病毒药物递送缺陷的悖论。
The Paradox of HIV Blood-Brain Barrier Penetrance and Antiretroviral Drug Delivery Deficiencies.
机构信息
University of Miami Miller School of Medicine, Department of Biochemistry and Molecular Biology, Miami, FL, USA.
University of Miami Miller School of Medicine, Department of Biochemistry and Molecular Biology, Miami, FL, USA; Dr JT Macdonald Foundation Biomedical Nanotechnology Institute of the University of Miami, Miami, FL, USA.
出版信息
Trends Neurosci. 2020 Sep;43(9):695-708. doi: 10.1016/j.tins.2020.06.007. Epub 2020 Jul 15.
HIV attacks the body's immune cells, frequently compromises the integrity of the blood-brain barrier (BBB), and infects the CNS in the early stages of infection. Dysfunction of the BBB further potentiates viral replication within the CNS, which can lead to HIV-associated neuropathology. Antiretroviral therapy (ART) significantly improves HIV patient outcomes and reduces mortality rates. However, there has been limited progress in targeting latent viral reservoirs within the CNS, which may eventually lead to rebound viremia. While ART drugs are shown to be effective in attenuating HIV replication in the periphery, the protection of the brain by the BBB offers an isolated sanctuary to harbor HIV and maintains chronic and persistent replication within the CNS. In this review, we elucidate the pathology of the BBB, its ability to potentiate viral replication, as well as current therapies and insufficiencies in treating HIV-infected individuals.
HIV 攻击人体的免疫细胞，经常损害血脑屏障（BBB）的完整性，并在感染的早期感染中枢神经系统。BBB 的功能障碍进一步增强了 CNS 内的病毒复制，从而导致与 HIV 相关的神经病理学。抗逆转录病毒疗法（ART）显著改善了 HIV 患者的预后并降低了死亡率。然而，针对 CNS 内潜伏性病毒库的治疗方法进展有限，这可能最终导致病毒血症反弹。虽然 ART 药物已被证明可有效抑制外周血中的 HIV 复制，但 BBB 对大脑的保护为 HIV 提供了一个隔离的庇护所，并维持了 CNS 内的慢性和持续性复制。在这篇综述中，我们阐明了 BBB 的病理学，其增强病毒复制的能力，以及当前治疗 HIV 感染者的疗法和不足之处。
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